Cancer remains a leading cause of death worldwide, with melanoma, ovarian, breast, prostate and colorectal cancer (CRC) being some of the most widely represented. In many cancers, metastasis is evidence of an advanced stage of cancer, and therefore a generally worse prognosis for the patient. As an example, CRC progresses through multiple distinct stages. Morphologically, inappropriate proliferation and anti-apoptosis cause formation of adenomas, which evolve into pre-invasive carcinoma in situ. Then, pre-invasive CRCs acquire the ability to invade through the submucosa and muscularis, metastasize, and survive outside the colon microenvironment niche. As 5-year survival for early stage CRC is ˜90% vs. ˜10% for metastatic CRC, understanding the mechanisms that regulate the transition from indolent (adenomas and carcinoma in situ) to locally invasive early clinical stage (stage I-II) and metastatic later stage (stage III/IV) CRC, as well as the stages of other metastatic cancers, is critical to improving patient outcomes. However, currently available models of cancer, such as subcutaneous xenografts which are widely used for drug screening and tumorigenicity studies do not recapitulate the tumor microenvironment of patients and seldom metastasize, which may partially explain the high rate of failure for clinical trials based on drugs identified using such models. Further, tail vein injection of cancer cells is sometimes used instead of xenografts, but this frequently does not result in optimally relevant tumor modeling. For example, tail vein injected CRC cells largely form lung tumors directly instead of gastrointestinal tumors, and while injection of CRC cells into spleen or under the kidney capsule can cause tumor formation in multiple organs, the tumors do not follow the clinical CRC metastases route. Further, it is feasible to surgically implant tumor cells to create a surgical orthotopic model, such as by implanting CRC cells into the gastrointestinal tract, but this requires highly trained technicians, is time-consuming, causes needless waste of animals who often do not survive the procedure and importantly does not robustly generate multiple liver metastasis, making such models unsuitable for drug discovery. Further still, all of these techniques require surgical procedures which create wounds and inflammation which can cause artifacts that can confound metastasis studies. Finally, while there are a number of genetically engineered animals that can form orthotopic tumors, these are typically confined to studying early events in tumorigenesis, are difficult and time consuming to make, and can have multiple significant genetic and epigenetic distinctions that make their tumors and metastatic events materially different from the human cancers they are intended to model. Thus, there is an ongoing need for improved methods, model cells and animals for use in developing improved treatments and prophylactic approaches for cancer and metastasis. The present disclosure addresses these and other needs.